Insulin and diet-induced changes in the ubiquitin-modified proteome of rat liver

Shilpa R Nagarajan; Amanda E Brandon; Jessie A McKenna; Harrison C Shtein; Thinh Q Nguyen; Eurwin Suryana; Philip Poronnik; Gregory J Cooney; Darren N Saunders; Andrew J Hoy

doi:10.1371/journal.pone.0174431

Insulin and diet-induced changes in the ubiquitin-modified proteome of rat liver

PLoS One. 2017 Mar 22;12(3):e0174431. doi: 10.1371/journal.pone.0174431. eCollection 2017.

Authors

Shilpa R Nagarajan¹, Amanda E Brandon^{2

3}, Jessie A McKenna^{4

5}, Harrison C Shtein¹, Thinh Q Nguyen¹, Eurwin Suryana², Philip Poronnik¹, Gregory J Cooney^{2

3}, Darren N Saunders^{4

5}, Andrew J Hoy¹

Affiliations

¹ Discipline of Physiology, School of Medical Sciences & Bosch Institute, Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia.
² Diabetes and Metabolism Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
³ St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
⁴ Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
⁵ School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.

Abstract

Ubiquitin is a crucial post-translational modification regulating numerous cellular processes, but its role in metabolic disease is not well characterized. In this study, we identified the in vivo ubiquitin-modified proteome in rat liver and determined changes in this ubiquitome under acute insulin stimulation and high-fat and sucrose diet-induced insulin resistance. We identified 1267 ubiquitinated proteins in rat liver across diet and insulin-stimulated conditions, with 882 proteins common to all conditions. KEGG pathway analysis of these proteins identified enrichment of metabolic pathways, TCA cycle, glycolysis/gluconeogenesis, fatty acid metabolism, and carbon metabolism, with similar pathways altered by diet and insulin resistance. Thus, the rat liver ubiquitome is sensitive to diet and insulin stimulation and this is perturbed in insulin resistance.

MeSH terms

Animals
Carbon / metabolism
Citric Acid Cycle / drug effects
Diet / methods
Dietary Fats / administration & dosage*
Fatty Acids / metabolism
Gluconeogenesis / drug effects
Glycolysis / drug effects
Insulin / administration & dosage*
Insulin Resistance / physiology
Lipid Metabolism / drug effects
Liver / drug effects*
Male
Metabolic Networks and Pathways / drug effects
Protein Processing, Post-Translational / drug effects
Proteome / drug effects*
Rats
Rats, Wistar
Sucrose / administration & dosage*
Ubiquitin / metabolism*

Substances

Dietary Fats
Fatty Acids
Insulin
Proteome
Ubiquitin
Sucrose
Carbon

Grants and funding

AJH is supported by a Helen and Robert Ellis Postdoctoral Research Fellowship from the Sydney Medical School Foundation and funding from the University of Sydney. DNS is supported by the National Health and Medical Research Council (project grant GNT1052963), a Neale Daniher MND Research Grant from the Motor Neurone Disease Research Institute of Australia, Guest Family Fellowship, and Mostyn Family Foundation.